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PMID: 12183361 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis.

Genes & development ·Vol. 16 ·No. 16 ·2002-08-15 ·Pages 2058-72

Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze'ev A

Abstract

beta-catenin and plakoglobin (gamma-catenin) are homologous molecules involved in cell adhesion, linking cadherin receptors to the cytoskeleton. beta-catenin is also a key component of the Wnt pathway by being a coactivator of LEF/TCF transcription factors. To identify novel target genes induced by beta-catenin and/or plakoglobin, DNA microarray analysis was carried out with RNA from cells overexpressing either protein. This analysis revealed that Nr-CAM is the gene most extensively induced by both catenins. Overexpression of either beta-catenin or plakoglobin induced Nr-CAM in a variety of cell types and the LEF/TCF binding sites in the Nr-CAM promoter were required for its activation by catenins. Retroviral transduction of Nr-CAM into NIH3T3 cells stimulated cell growth, enhanced motility, induced transformation, and produced rapidly growing tumors in nude mice. Nr-CAM and LEF-1 expression was elevated in human colon cancer tissue and cell lines and in human malignant melanoma cell lines but not in melanocytes or normal colon tissue. Dominant negative LEF-1 decreased Nr-CAM expression and antibodies to Nr-CAM inhibited the motility of B16 melanoma cells. The results indicate that induction of Nr-CAM transcription by beta-catenin or plakoglobin plays a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility.

MeSH Terms
3T3 Cells Animals Base Sequence Binding Sites Blotting, Northern Blotting, Western Cell Adhesion Cell Adhesion Molecules/genetics,metabolism,physiology Cell Line Cell Membrane/metabolism Cell Movement Colonic Neoplasms/metabolism Cytoskeletal Proteins/biosynthesis,metabolism DNA-Binding Proteins/biosynthesis Desmoplakins Genes, Dominant Humans Luciferases/metabolism Lymphoid Enhancer-Binding Factor 1 Male Melanoma/metabolism Mice Mice, Nude Microscopy, Fluorescence Molecular Sequence Data Oligonucleotide Array Sequence Analysis Plasmids/metabolism Promoter Regions, Genetic Protein Binding Protein Biosynthesis RNA/metabolism Retroviridae/genetics Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors Trans-Activators/biosynthesis,metabolism Transcription Factors/biosynthesis Transcriptional Activation Transduction, Genetic Transfection Tumor Cells, Cultured Wound Healing beta Catenin gamma Catenin
Chemicals
CTNNB1 protein, human CTNNB1 protein, mouse Cell Adhesion Molecules Cytoskeletal Proteins DNA-Binding Proteins Desmoplakins JUP protein, human Jup protein, mouse LEF1 protein, human Lef1 protein, mouse Lymphoid Enhancer-Binding Factor 1 NRCAM protein, human Nrcam protein, mouse Trans-Activators Transcription Factors beta Catenin gamma Catenin RNA Luciferases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Conacci-Sorrell Maralice E
Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Ben-Yedidia Tamar
Shtutman Michael
Feinstein Elena
Einat Paz
Ben-Ze'ev Avri
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.227502
Published
2002-08-15
Pages
2058-72
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC186445
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.227502 PMC Full Text View journal details
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